Microfluidics refers to a set of technologies involving the flow of fluids through channels having at least one linear interior dimension, such as depth or radius, of less than 1 mm. It is possible to create microscopic equivalents of bench-top laboratory equipment such as beakers, pipettes, incubators, electrophoresis chambers, and analytical instruments within the channels of a microfluidic device. Since it is also possible to combine the functions of several pieces of equipment on a single microfluidic device, a single microfluidic device can perform a complete analysis that would ordinarily require the use of several pieces of laboratory equipment. A microfluidic device designed to carry out a complete chemical or biochemical analysis is commonly referred to as a micro-Total Analysis System (μ-TAS) or a “lab-on-a chip.”
A lab-on-a-chip type microfluidic device, which can simply be referred to as a “chip,” is typically used as a replaceable component, like a cartridge or cassette, within an instrument. The chip and the instrument form a complete microfluidic system. The instrument can be designed to interface with microfluidic devices designed to perform different assays, giving the system broad functionality. For example, the commercially available Agilent 2100 Bioanalyzer system can be configured to interface with four different types of assays, namely, DNA (deoxyribonucleic acid), RNA (ribonucleic acid), protein and cell assays, by simply placing the appropriate type of chip into the instrument.
In a typical microfluidic system, all of the microfluidic channels are in the interior of the chip. The instrument can interface with the chip by performing a variety of different functions: supplying the driving forces that propel fluid through the channels in the chip, monitoring and controlling conditions (e.g., temperature) within the chip, collecting signals emanating from the chip, introducing fluids into and extracting fluids out of the chip, and possibly many others. The instruments are typically computer controlled so that they can be programmed to interface with different types of chips and to interface with a particular chip in such a way as to carry out a desired analysis.
Microfluidic devices designed to carry out complex analyses will often have complicated networks of intersecting channels with some of the channels being open to the outside of the microfluidic devices through one or more wells. Performing the desired assay on such chips will often involve separately controlling the flows through certain channels and selectively directing flows from certain channels through channel intersections. Fluid flow through complex interconnected channel networks can be accomplished by either building microscopic pumps and valves into the chip or applying a combination of driving forces to the channels. The use of multiple electrical or pressure driving forces to control flow in a chip eliminates the need to fabricate valves and pumps on the chip itself, thus simplifying chip design and lowering chip cost.
Lab-on-a-chip type microfluidic devices offer a variety of inherent advantages over conventional laboratory processes such as reduced consumption of sample and reagents, ease of automation, large surface-to-volume ratios, and relatively fast reaction times. Thus, microfluidic devices have the potential to perform diagnostic assays more quickly, reproducibly, and at a lower cost than conventional devices. The advantages of applying microfluidic technology to diagnostic applications were recognized early on in development of microfluidics. For example, microfluidic systems exist in which the steps of sample preparation, PCR (polymerase chain reaction) amplification, and analyte detection are carried out on a single chip.
Many chemical and biochemical analyses require use of beads or other loose material in the process stream. One example is the use of beads to extract a component of interest from a raw biological sample. A core of the bead is coated with a ligand that specifically binds to the component of interest, which can then be removed from the bead. The beads provide an increased surface area with which components in a fluid flowing through the beads can interact. Small beads can be packed more closely than large beads, providing more surface area per unit volume. Beads can be used in the wells of microfluidic devices but must be large enough to avoid being swept into the channels. This limits the packing density that can be achieved and the amount of reaction that can take place in a given volume of the chip. In addition, beads entering the channels can enter the process in undesirable places and can clog flow channels.
It would be desirable to have a microfluidic device with a filter that would overcome the above disadvantages.